The Adult Respiratory Distress Syndrome is characterized by an accumulation of phagocytes (primarily neutrophils and mononuclear phagocytes) in the alveolar space. The emigration of phagocytes from the pulmonary microcirculation to the alveolus required the interaction of leukocyte adhesion molecules with endothelial ligands, matrix components, and epithelial ligands. Although critical for host defense and repair, phagocytes have been implicated as important mediators of alveolar- capillary injury in ARDS. Inhibition of phagocyte adhesion has the potential to reduce acute lung injury by preventing phagocyte-mediated damage to endothelium and epithelium or by down-modulating adhesion- dependent phagocyte functions. This proposal will examine the mechanisms and consequences of phagocyte adhesion in acute lung injury in the following Specific Aims: 1) to determine the role of integrin and selectin receptors in phagocyte emigration in acute lung inflammation; 2) to determine the effect of inhibiting integrin and selectin receptors on alveolar-capillary injury in a model of sepsis; 3) to determine the role of alveolar macrophage adhesion receptors in inflammatory gene expression; and 4) to examine the expression of activation markers and adhesion molecules on leukocytes in whole blood specimens obtained from patients with trauma and sepsis. It is hoped that these studies will lead to the development of "anti-adhesion" therapy as a new approach to the treatment of ARDS.